The general aim in particular of biochemical analysis processes is to identify biochemical molecules, for example DNA sequences, proteins, haptenes and antigens. By way of example, probe molecules which are immobilized on a substrate within an analysis area are brought into contact with an analyte solution which contains the biochemical molecules or structures which have been mentioned (referred to for short in the following text as target molecules). Target molecules which match one another on the basis of the lock-and-key principle are, for example, bonded to a probe molecule forming bonded pairs of probe molecules. The occurrence of such reaction events is detected, for example optically or electrically, with the aid of labels or markers which are provided on the target molecules.
In addition to markers which can be detected in this way, magnetic marker particles are also used. In these cases, a homogeneous magnetic field acting on the analysis area is produced, and stray fields caused by the magnetic marker particles are detected with the aid of electromagnetic sensors.
The literature publication “Biosensor based on force microscope technology” from J. Vac. Sci. Technology B 14(2), March/April 1996, P. 789 pp. describes a biosensor, in which mechanical oscillating bars, that is to say commercial piezo-electric scanning probe measurement tips are used for detection of magnetically induced forces. After a biological reaction, in particular for DNA identification, magnetic markers are left behind on the oscillating bar, and the change in the oscillation response to a variable magnetic force is used as a measure of the number of magnetic markers, and thus of the biological reaction. The magnetic field is produced by permanent magnets and a Helmholtz coil pair. Sensitive measurements in a liquid medium are not possible by means of oscillating bars.
U.S. Pat. No. 5,981,297 A describes the detection of selectively deposited molecules with magnetic markers by means of GMR sensors. The sensors can be used to obtain information about the concentration of the target molecules. In this case, it should be noted that there are no further-reaching analyses or means for carrying out the removal of markers which have not been bonded by means of a magnetic force. U.S. Pat. No. 6,180,418 B1 describes arrangements of moving permanent magnets by means of which magnetic markers (so-called beads) are moved during the course of an assay process. The beads are detected optically. Unbonded beads are removed by the application of a previously calculated force gradient, that is to say mechanical movement of the magnets. The biological bonding forces are not determined. Furthermore WO 00/61803 A1 describes a process using a cleaning step with magnetic forces. However, it is not possible to determine the biological bonding forces beyond the cleaning force of lpN, in this case. The detection and manipulation of biomolecules with magnetic particles (magnetic beads) are known from US 2004/0219695 A1. Magnets are moved backwards and forwards for this purpose.
U.S. Pat. No. 5,445,970 A describes a manually controlled balance of chemical and magnetic forces. The beads are detected optically. Little attention is paid to the magnetic design, and standard versions appear to be adequate. A GMI sensor for detection of magnetic markers is described in WO 02/29430 A1. In this case, the external magnetic field must have a constant magnitude in order to allow the GMI effect to be used. Bonding forces therefore cannot be determined. In this case, the beads are detected optically. Manipulators operating using magnetic beads are likewise known from DE 100 50 029 A1.
Finally, US 2005/0087000 A1 discloses a process, major parts of which are equivalent to the BARC sensor from U.S. Pat. No. 5,981,297A. The difference is the use of considerably smaller beads, which result in better measurement sensitivity. GMR sensors, in particular, are used to measure the density per unit area of the beads and to measure very small magnetic-field changes. Magnetic fields are produced by a coil pair.